The search for the molecule or molecules responsible for the bone-, cartilage-, and other connective tissue-inductive activity present in bone and other tissue extracts has led to the discovery and identification of a several groups of molecules, such as the Bone Morphogenetic Proteins (BMPs). The unique inductive activities of these proteins, along with their presence in bone, suggests that they are important regulators of bone repair processes, and may be involved in the normal maintenance of bone tissue. There is a need to identify whether additional proteins, particularly human proteins, exist which play a role in these processes. It has recently been reported that Xenopus chordin is a molecule which contributes to dorsoventral patterning by binding to BMP-4. Piccolo et al., Cell, 86:589-98 (1996). The present invention relates to the identification of such a novel human protein, which the inventors have designated human chordin.
Human chordin is the human homolog of a xenopus protein called chordin. The nucleotide and amino acid sequences of xenopus chordin are described in Lasai et al., Cell, 79:779-790 (1994). The xenopus chordin gene has been described as being expressed in the frog embryo head, trunk and tail organizer regions during gastrulation, and as being capable of inducing secondary axes in frog embryos, and rescuing axis formation in ventralized frog, as well as modifying mesoderm induction. Ibid. In addition, xenopus chordin has been shown to induce anterior neural markers in the absence of mesoderm induction. Sashai et al., Nature, 376:333-336 (1995).